These studies aim to determine whether the sensitivity of GH secretory mechanisms to IGF-I negative feedback differs in young and older adults, and, using pyridostigmine (a drug thought to inhibit somatostatin secretion), whether suppression of somatostatin is involved in this negative feedback effect of IGF-I. Study completed, abstract presented 1996, manuscript to be submitted for publication to J Clin Endocrinol Metab. Eleven young adults (6 men, 5 women), received 4-h iv infusions of rhIGF-I (3 ug/kg/h) or saline from 25.5-29.5 h of a 47.5 h fast. A glucose clamp was used to prevent blood glucose levels decreasing more than 15% below baseline. Serum GH was suppressed by rhIGF-I infusion within 2 h of its commencement, was maximal in the hr after the end of the infusion and then rapidly resolved. The close temporal association between the resolution of GH suppression and fall of free IGF-I concentrations, and the lack of any clear association with total IGF-I concentrations, suggests that unbound (free) and not protein bound IGF-I is the major IGF-I component responsible for this suppression.